Structure of the Ligand Gated Acetylcholine Receptor

Unlike the Na+ channel, which consists of a single polypeptide chain with four homologous domains (each of which has six membrane-spanning regions; see Chapter 4, Fig. 14), the cation channel of the ACh receptor consists of five subunits, four of which are from separate gene products. The subunits have been designated a, ß, y, e, and <5, and in fetal muscle are arranged in the stoichiometry of a2ßyS (Fig. 12A,B), whereas in adult muscle the stoichiometry is a2ße< . The subunits are approximately 50% homologous at the amino acid level, indicating that they evolved from a common ancestral gene. A common feature to all subunits is their four membrane-spanning regions (designated M1 to M4; Fig. 12B,C). The pore of the channel is believed to be formed by the proper alignment of the M2 regions of each of the five subunits (Fig. 12B). A key difference between the a subunit and the other subunits is its

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